Previous work on the role of immune complexes in the pathogenesis of systemic loupus erythematosus (SLE), rheumatoid arthritis (RA) and related disorders will be continued. In studies on SLE, primary emphasis will be placed on the characterization of the DNA and anti-native DNA (nDNA) antibodies in low molecular weight serum DNA-anti DNA complexes that occur during disease activity in association with elevated titers of nDNA antibodies and hypocomplementemia. The relationship of these complexes to hypocomplementemia will be determined by complement fixation studies. Uniqueness of both the antigen and antibody will be sought by comparative binding studies and studying cross idiotypes which may be present among the nDNA antibodies. These studies may not only provide insights to the pathogenesis of SLE but are of practical clinical importance in using serologic tests for the management of patients with SLE. In RA the primary goal will be to explore the role of rheumatoid factors with distinct cross idiotypes. The incidence and relative amounts of rheumatoid factor with the three known cross idiotypes will be determined in populations of patients with RA. The relationship of these rheumatoid factors to the serum immune complexes which occur in the disease will be determined. In addition, unique antigens reactive with these rheumatoid factors and anti-idiotype antibody will be sought in these complexes. It will also be determined if cross idiotypes in man, as in the mouse, are under genetic control. This will be done by determining cross idiotypes and IgG allotypes in pedigrees that have been shown to have rheumatoid factors in multiple family members. These studies may provide new insights to both etiologic and genetic factors in RA.